Dissertationshttp://hdl.handle.net/2022/30862015-03-31T20:46:16Z2015-03-31T20:46:16ZA STUDY OF HOST-CHLAMYDIAL INTERACTIONS MEDIATED BY INTERFERON-GAMMA AND NITRIC OXIDERajaram, Krithikahttp://hdl.handle.net/2022/196972015-03-06T17:30:26Z2015-02-01T00:00:00ZA STUDY OF HOST-CHLAMYDIAL INTERACTIONS MEDIATED BY INTERFERON-GAMMA AND NITRIC OXIDE
Rajaram, Krithika
The host response towards chlamydial infection mobilizes elements of both innate and adaptive immunity, culminating in the production of the Th1 cytokine interferon-gamma (IFN-&#947;). IFN-&#947; induces a variety of anti-chlamydial programs, many of which are unique to either humans or mice. Consequently, the human pathogen Chlamydia trachomatis and its near-identical murine relative C. muridarum have evolved to survive and cause disease in their respective hosts. Understanding the mechanisms that contribute to chlamydial niche specificity will facilitate the creation of improved mouse models for the study of human chlamydial disease. To this end, we examined a small chlamydial genomic region of extreme divergence called the Plasticity Zone (PZ) in C. muridarum for its alleged roles in host specificity and virulence. Using a newly adapted reverse genetic technique, we determined that much of the PZ is in fact dispensable in the murine genital tract. We concomitantly embarked on a screen for C. muridarum mutants that were no longer resistant to IFN-&#947; and uncovered a gain-of-function mutation in an orf outside the PZ that led to dramatic attenuation in mice.
IFN-&#947; is secreted by multiple cell types including macrophages, which participate in innate as well as adaptive immune responses. IFN&#947;-dependent and -independent defense mechanisms mounted by macrophages contribute significantly to bacterial clearance. Specifically, the amount of nitric oxide (NO) produced by macrophages in response to different infectious doses determines infection outcome in mice. We discovered that the in vivo regulation of infection by NO is also replicated in cell culture. Murine macrophage cell lines infected at high multiplicities of infection cause chlamydial death because of a massive NO response that is triggered by elevated levels of reactive oxygen species (ROS) and lysosomal cathepsin B activity.
Taken together, our work elucidates the mechanisms behind important host and chlamydial defense strategies, offering insight into the evolutionary adaptations that are a consequence of the relentless host-pathogen arms race.
Thesis (Ph.D.) - Indiana University, Biology, 2015
2015-02-01T00:00:00ZNEURONAL ADAPTATIONS IN THE NUCLEUS ACCUMBENS CORE UNDER ACUTE AND CHRONIC EXPOSURE TO CANNABINOIDSLee, Sung Hahttp://hdl.handle.net/2022/196962015-03-09T13:45:08Z2015-02-01T00:00:00ZNEURONAL ADAPTATIONS IN THE NUCLEUS ACCUMBENS CORE UNDER ACUTE AND CHRONIC EXPOSURE TO CANNABINOIDS
Lee, Sung Ha
Cannabis, known as marijuana, is the most commonly used illicit drug in the United States, but we have limited knowledge about its effects on the brain, particularly the reward circuitry. Cannabinoids, the psychoactive ingredient of cannabis, activate cannabinoid receptors in the mesolimbic area, resulting in increased dopamine transmission in the nucleus accumbens (NAc). This effect is believed to enhance goal-directed behavioral responses, including the motivation to obtain natural and drug rewards, but NAc signaling under cannabinoid exposure remain largely unknown. To address this gap, this dissertation work examines two main signaling changes in the NAc core: neuronal activities and dopamine dynamics.
Since cannabis derivatives are usually used for a prolonged time, ongoing changes in the NAc core were investigated in response to acute and repeated exposure of cannabinoids. Therefore, in Experiment 1, NAc neuronal signaling was obtained on initial and repeated exposure (seven daily injections) of a cannabinoid receptor agonist, CP55,940 (0.2 mg/kg or 0.4 mg/kg) in male Sprague-Dawley rats using an in vivo electrophysiology technique. The overall effect of CP55,940 on CB1/2 receptor activation acutely inhibited NAc neuron activity and reduced correlated neuronal activity/burst firing, and these effects lasted for the seven days of injections. This result suggests that cannabinoids reduce neuronal signaling and disrupt functional communication in the NAc core for a prolonged period. However, cannabinoid increased the theta power of local field potentials after acute CP55,940 injection but repeated treatment failed to maintain this effect.
In Experiment 2, the electrically evoked dopamine overflow was collected using fast scan cyclic voltammetry (FSCV). Using kinetic analysis, dopamine release and reuptake were assessed immediately following one or seven daily injections of CP55,940 (0.2 mg/kg, i.p.) or a vehicle. A single injection of CP55,940 increased the stimulation-evoked dopamine concentration without altering dopamine reuptake. However, repeated CP55,940 exposure led to a similar level of dopamine concentration as the chronic vehicle treatment.
The sustained neuronal signaling but altered dopamine dynamics in the NAc core after repeated cannabinoid exposure suggest separate mechanisms in the development of tolerance. As the present results indicate, altered signaling of the NAc core could provide evidence of changes in motivational states that, in turn, may play a role in changing reward-related behaviors.
Thesis (Ph.D.) - Indiana University, Neuroscience, 2015
2015-02-01T00:00:00ZAN EXPLORATION OF TAIWANESE ADOLESCENT CROSS-STRAIT TRANSMIGRATION, EDUCATION, AND IDENTIFICATIONWang, Hsiang-ninghttp://hdl.handle.net/2022/196842015-03-16T16:30:12Z2015-02-01T00:00:00ZAN EXPLORATION OF TAIWANESE ADOLESCENT CROSS-STRAIT TRANSMIGRATION, EDUCATION, AND IDENTIFICATION
Wang, Hsiang-ning
This dissertation explores the identification of Taiwanese adolescents with Taiwan and/or China as a process and outcome of cross-Strait transmigration. Given their explicit or implicit identification with Taiwan, and their need to accommodate Chinese social norms, transmigrant youth are identified as "third culture kids," not belonging fully to either culture but to an in-between status and location that they have been forced to negotiate. From political, societal, and cultural perspectives, this dissertation analyzes how identity is legitimized, contested, and negotiated through the dynamic interplay among institutional sources of power such as the state and schools, public discourses on cross-Strait relations, social interactions among individuals, and individual subjectivity. Drawing on data from a one-year multi-sited ethnographic study in both Mainland China and Taiwan, this dissertation reveals the lived experiences of Taiwanese transmigrant youth by addressing political and ideological challenges, disparity of social norms and status, and cultural challenges and opportunities they encounter in their large social and educational ecology composed of family, school, community, and cross-Strait societies. The daily identification practices and performances of these young Taiwanese transmigrants shape an integrated and collective Taiwanese identity closely connected to a strong awareness of and response to cultural, political and normative differences between themselves and the Chinese they come to know and interact with on the Mainland; their respect for their host country is generally limited to its economic power. Transmigrant youths show diverse individual differences in their identification with Taiwan and China as seen in their selective assimilation, accommodation, and resistance, which are unsettled and changing. The complexities behind their identification with Taiwan are reflected in their shifting use of languages and behaviors based on varied circumstances that can be characterized as expressions of political defensive identity, differentiated identity, coexisting romanticized and pragmatic identity, class identity, and youth culture identity.
Thesis (Ph.D.) - Indiana University, School of Education, 2015
2015-02-01T00:00:00ZScalable Architecture for Integrated Batch and Streaming Analysis of Big DataGao, Xiaominghttp://hdl.handle.net/2022/196822015-03-05T23:30:31Z2015-02-01T00:00:00ZScalable Architecture for Integrated Batch and Streaming Analysis of Big Data
Gao, Xiaoming
As Big Data processing problems evolve, many modern applications demonstrate special characteristics. Data exists in the form of both large historical datasets and high-speed real-time streams, and many analysis pipelines require integrated parallel batch processing and stream processing. Despite the large size of the whole dataset, most analyses focus on specific subsets according to certain criteria. Correspondingly, integrated support for efficient queries and post- query analysis is required.
To address the system-level requirements brought by such characteristics, this dissertation proposes a scalable architecture for integrated queries, batch analysis, and streaming analysis of Big Data in the cloud. We verify its effectiveness using a representative application domain - social media data analysis - and tackle related research challenges emerging from each module of the architecture by integrating and extending multiple state-of-the-art Big Data storage and processing systems.
In the storage layer, we reveal that existing text indexing techniques do not work well for the unique queries of social data, which put constraints on both textual content and social context. To address this issue, we propose a flexible indexing framework over NoSQL databases to support fully customizable index structures, which can embed necessary social context information for efficient queries.
The batch analysis module demonstrates that analysis workflows consist of multiple algorithms with different computation and communication patterns, which are suitable for different processing frameworks. To achieve efficient workflows, we build an integrated analysis stack based on YARN, and make novel use of customized indices in developing sophisticated analysis algorithms.
In the streaming analysis module, the high-dimensional data representation of social media streams poses special challenges to the problem of parallel stream clustering. Due to the sparsity of the high-dimensional data, traditional synchronization method becomes expensive and severely impacts the scalability of the algorithm. Therefore, we design a novel strategy that broadcasts the incremental changes rather than the whole centroids of the clusters to achieve scalable parallel stream clustering algorithms.
Performance tests using real applications show that our solutions for parallel data loading/indexing, queries, analysis tasks, and stream clustering all significantly outperform implementations using current state-of-the-art technologies.
Thesis (Ph.D.) - Indiana University, Computer Sciences, 2015
2015-02-01T00:00:00Z